Although stochasticity in oceanographic conditions is known to be an important driver of temporal genetic change in many marine species, little is known about whether genetically distinct plankton ...populations can persist in open ocean habitats. A prior study demonstrated significant population genetic structure among oceanic gyres in the mesopelagic copepod Haloptilus longicornis in both the Atlantic and Pacific Oceans, and we hypothesized that populations within each gyre represent distinct gene pools that persist over time. We tested this expectation through basin-scale sampling across the Atlantic Ocean in 2010 and 2012. Using both mitochondrial (mtCOII) and microsatellite markers (7 loci), we show that the genetic composition of populations was stable across two years in both the northern and southern subtropical gyres. Genetic variation in this species was partitioned among ocean gyres (FCT = 0.285, P < 0.0001 for mtCOII, FCT = 0.013, P < 0.0001 for microsatellites), suggesting strong spatial population structure, but no significant partitioning was found among sampling years. This temporal persistence of population structure across a large geographic scale was coupled with chaotic genetic patchiness at smaller spatial scales, but the magnitude of genetic differentiation was an order of magnitude lower at these smaller scales. Our results demonstrate that genetically distinct plankton populations persist over time in highly-dispersive open ocean habitats, and this is the first study to rigorously test for temporal stability of large scale population structure in the plankton.
Familial multiple endocrine neoplasia type 1 (FMEN1) is an autosomal dominant disorder characterized by tumors of the parathyroid glands, pancreatic islets, and anterior pituitary. The gene for this ...disease maps to chromosome 11q12-11q13, and allelic loss in this region has been shown in both sporadic and FMEN1-related parathyroid tumors. FMEN1-related pancreatic islet tumors, and rarely in sporadic anterior pituitary tumors. We tested for allelic loss at 7 loci on chromosome 11 in 17 tumors outside the parathyroid. We found loss of heterozygosity in 2 of 2 FMEN1-related benign pancreatic islet tumors but in none of 8 informative sporadic islet tumors (P = 0.02) including 5 malignant gastrinomas. Of 3 islet tumors from patients who had some but not all features of FMEN1, one showed allelic loss for 5 of 5 informative restriction fragment length polymorphisms, and the other 2 retained heterozygosity for all informative markers. A bronchial carcinoid from an FMEN1 patient and 3 sporadic anterior pituitary tumors showed no allelic loss. These data provide new evidence that many sporadic pancreatic islet neoplasms, even when malignant, do not develop through homozygous inactivation of the MEN1 gene.
Purpose: There has been increased interest in using telepractice for involving more diverse children in research and clinical services, as well as when in-person assessment is challenging, such as ...during COVID-19. Little is known, however, about the feasibility, reliability, and validity of language samples when conducted via telepractice. Method: Child language samples from parent-child play were recorded either in person in the laboratory or via video chat at home, using parents' preferred commercially available software on their own device. Samples were transcribed and analyzed using Systematic Analysis of Language Transcripts software. Analyses compared measures between-subjects for 46 dyads who completed video chat language samples versus 16 who completed in-person samples; within-subjects analyses were conducted for a subset of 13 dyads who completed both types. Groups did not differ significantly on child age, sex, or socioeconomic status. Results: The number of usable samples and percent of utterances with intelligible audio signal did not differ significantly for in-person versus video chat language samples. Child speech and language characteristics (including mean length of utterance, type-token ratio, number of different words, grammatical errors/omissions, and child speech intelligibility) did not differ significantly between in-person and video chat methods. This was the case for between-group analyses and within-child comparisons. Furthermore, transcription reliability (conducted on a subset of samples) was high and did not differ between in-person and video chat methods. Conclusions: This study demonstrates that child language samples collected via video chat are largely comparable to in-person samples in terms of key speech and language measures. Best practices for maximizing data quality for using video chat language samples are provided.
The conversion of white adipocytes to thermogenic beige adipocytes represents a potential mechanism to treat obesity and related metabolic disorders. However, the mechanisms involved in converting ...white to beige adipose tissue remain incompletely understood. Here we show profound beiging in a genetic mouse model lacking the transcriptional repressor Krüppel-like factor 3 (KLF3). Bone marrow transplants from these animals confer the beige phenotype on wild type recipients. Analysis of the cellular and molecular changes reveal an accumulation of eosinophils in adipose tissue. We examine the transcriptomic profile of adipose-resident eosinophils and posit that KLF3 regulates adipose tissue function via transcriptional control of secreted molecules linked to beiging. Furthermore, we provide evidence that eosinophils may directly act on adipocytes to drive beiging and highlight the critical role of these little-understood immune cells in thermogenesis.
Individuals with dementia or mild cognitive impairment frequently have multiple chronic conditions (defined as ≥2 chronic medical conditions) and take multiple medications, increasing their risk for ...adverse outcomes. Deprescribing (reducing or stopping medications for which potential harms outweigh potential benefits) may decrease their risk of adverse outcomes.
To examine the effectiveness of increasing patient and clinician awareness about the potential to deprescribe unnecessary or risky medications among patients with dementia or mild cognitive impairment.
This pragmatic, patient-centered, 12-month cluster randomized clinical trial was conducted from April 1, 2019, to March 31, 2020, at 18 primary care clinics in a not-for-profit integrated health care delivery system. The study included 3012 adults aged 65 years or older with dementia or mild cognitive impairment who had 1 or more additional chronic medical conditions and were taking 5 or more long-term medications.
An educational brochure and a questionnaire on attitudes toward deprescribing were mailed to patients prior to a primary care visit, clinicians were notified about the mailing, and deprescribing tip sheets were distributed to clinicians at monthly clinic meetings.
The number of prescribed long-term medications and the percentage of individuals prescribed 1 or more potentially inappropriate medications (PIMs). Analysis was performed on an intention-to-treat basis.
This study comprised 1433 individuals (806 women 56.2%; mean SD age, 80.1 7.2 years) in 9 intervention clinics and 1579 individuals (874 women 55.4%; mean SD age, 79.9 7.5 years) in 9 control clinics who met the eligibility criteria. At baseline, both groups were prescribed a similar mean (SD) number of long-term medications (7.0 2.1 in the intervention group and 7.0 2.2 in the control group), and a similar proportion of individuals in both groups were taking 1 or more PIMs (437 of 1433 individuals 30.5% in the intervention group and 467 of 1579 individuals 29.6% in the control group). At 6 months, the adjusted mean number of long-term medications was similar in the intervention and control groups (6.4 95% CI, 6.3-6.5 vs 6.5 95% CI, 6.4-6.6; P = .14). The estimated percentages of patients in the intervention and control groups taking 1 or more PIMs were similar (17.8% 95% CI, 15.4%-20.5% vs 20.9% 95% CI, 18.4%-23.6%; P = .08). In preplanned subgroup analyses, adjusted differences between the intervention and control groups were -0.16 (95% CI, -0.34 to 0.01) for individuals prescribed 7 or more long-term medications at baseline (n = 1434) and -0.03 (95% CI, -0.20 to 0.13) for those prescribed 5 to 6 medications (n = 1578) (P = .28 for interaction; P = .19 for subgroup interaction for PIMs).
This large-scale educational deprescribing intervention for older adults with cognitive impairment taking 5 or more long-term medications and their primary care clinicians demonstrated small effect sizes and did not significantly reduce the number of long-term medications and PIMs. Such interventions should target older adults taking relatively more medications.
ClinicalTrials.gov Identifier: NCT03984396.
There are increasing calls to provide greenspace in urban areas, yet the ecological quality, as well as quantity, of greenspace is important. Short mown grassland designed for recreational use is the ...dominant form of urban greenspace in temperate regions but requires considerable maintenance and typically provides limited habitat value for most taxa. Alternatives are increasingly proposed, but the biodiversity potential of these is not well understood. In a replicated experiment across six public urban greenspaces, we used nine different perennial meadow plantings to quantify the relative roles of floristic diversity and height of sown meadows on the richness and composition of three taxonomic groups: plants, invertebrates, and soil microbes. We found that all meadow treatments were colonized by plant species not sown in the plots, suggesting that establishing sown meadows does not preclude further locally determined grassland development if management is appropriate. Colonizing species were rarer in taller and more diverse plots, indicating competition may limit invasion rates. Urban meadow treatments contained invertebrate and microbial communities that differed from mown grassland. Invertebrate taxa responded to changes in both height and richness of meadow vegetation, but most orders were more abundant where vegetation height was longer than mown grassland. Order richness also increased in longer vegetation and Coleoptera family richness increased with plant diversity in summer. Microbial community composition seems sensitive to plant species composition at the soil surface (0–10 cm), but in deeper soils (11–20 cm) community variation was most responsive to plant height, with bacteria and fungi responding differently. In addition to improving local residents’ site satisfaction, native perennial meadow plantings can produce biologically diverse grasslands that support richer and more abundant invertebrate communities, and restructured plant, invertebrate, and soil microbial communities compared with short mown grassland. Our results suggest that diversification of urban greenspace by planting urban meadows in place of some mown amenity grassland is likely to generate substantial biodiversity benefits, with a mosaic of meadow types likely to maximize such benefits.
Whether arthroscopic partial meniscectomy for symptomatic patients with a meniscal tear and knee osteoarthritis results in better functional outcomes than nonoperative therapy is uncertain.
We ...conducted a multicenter, randomized, controlled trial involving symptomatic patients 45 years of age or older with a meniscal tear and evidence of mild-to-moderate osteoarthritis on imaging. We randomly assigned 351 patients to surgery and postoperative physical therapy or to a standardized physical-therapy regimen (with the option to cross over to surgery at the discretion of the patient and surgeon). The patients were evaluated at 6 and 12 months. The primary outcome was the difference between the groups with respect to the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical-function score (ranging from 0 to 100, with higher scores indicating more severe symptoms) 6 months after randomization.
In the intention-to-treat analysis, the mean improvement in the WOMAC score after 6 months was 20.9 points (95% confidence interval CI, 17.9 to 23.9) in the surgical group and 18.5 (95% CI, 15.6 to 21.5) in the physical-therapy group (mean difference, 2.4 points; 95% CI, -1.8 to 6.5). At 6 months, 51 active participants in the study who were assigned to physical therapy alone (30%) had undergone surgery, and 9 patients assigned to surgery (6%) had not undergone surgery. The results at 12 months were similar to those at 6 months. The frequency of adverse events did not differ significantly between the groups.
In the intention-to-treat analysis, we did not find significant differences between the study groups in functional improvement 6 months after randomization; however, 30% of the patients who were assigned to physical therapy alone underwent surgery within 6 months. (Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases; METEOR ClinicalTrials.gov number, NCT00597012.).
The COVID-19 pandemic has impacted data collection for longitudinal studies in developmental sciences to an immeasurable extent. Restrictions on conducting in-person standardized assessments have led ...to disruptive innovation, in which novel methods are applied to increase participant engagement. Here, we focus on remote administration of behavioral assessment. We argue that these innovations in remote assessment should become part of the new standard protocol in developmental sciences to facilitate data collection in populations that may be hard to reach or engage due to burdensome requirements (e.g., multiple in-person assessments). We present a series of adaptations to developmental assessments (e.g., Mullen) and a detailed discussion of data analytic approaches to be applied in the less-than-ideal circumstances encountered during the pandemic-related shutdown (i.e., missing or messy data). Ultimately, these remote approaches actually strengthen the ability to gain insight into developmental populations and foster pragmatic innovation that should result in enduring change.
More than 300,000 surgeries are performed annually in the United States for pelvic organ prolapse. Sacrospinous ligament fixation (SSLF) and uterosacral ligament suspension (ULS) are commonly ...performed transvaginal surgeries to correct apical prolapse. Little is known about their comparative efficacy and safety, and it is unknown whether perioperative behavioral therapy with pelvic floor muscle training (BPMT) improves outcomes of prolapse surgery.
To compare outcomes between (1) SSLF and ULS and (2) perioperative BPMT and usual care in women undergoing surgery for vaginal prolapse and stress urinary incontinence.
Multicenter, 2 × 2 factorial, randomized trial of 374 women undergoing surgery to treat both apical vaginal prolapse and stress urinary incontinence was conducted between 2008 and 2013 at 9 US medical centers. Two-year follow-up rate was 84.5%.
The surgical intervention was transvaginal surgery including midurethral sling with randomization to SSLF (n = 186) or ULS (n = 188); the behavioral intervention was randomization to receive perioperative BPMT (n = 186) or usual care (n = 188).
The primary outcome for the surgical intervention (surgical success) was defined as (1) no apical descent greater than one-third into vaginal canal or anterior or posterior vaginal wall beyond the hymen (anatomic success), (2) no bothersome vaginal bulge symptoms, and (3) no re-treatment for prolapse at 2 years. For the behavioral intervention, primary outcome at 6 months was urinary symptom scores (Urinary Distress Inventory; range 0-300, higher scores worse), and primary outcomes at 2 years were prolapse symptom scores (Pelvic Organ Prolapse Distress Inventory; range 0-300, higher scores worse) and anatomic success.
At 2 years, surgical group was not significantly associated with surgical success rates (ULS, 59.2% 93/157 vs SSLF, 60.5% 92/152; unadjusted difference, -1.3%; 95% CI, -12.2% to 9.6%; adjusted odds ratio OR, 0.9; 95% CI, 0.6 to 1.5) or serious adverse event rates (ULS, 16.5% 31/188 vs SSLF, 16.7% 31/186; unadjusted difference, -0.2%; 95% CI, -7.7% to 7.4%; adjusted OR, 0.9; 95% CI, 0.5 to 1.6). Perioperative BPMT was not associated with greater improvements in urinary scores at 6 months (adjusted treatment difference, -6.7; 95% CI, -19.7 to 6.2), prolapse scores at 24 months (adjusted treatment difference, -8.0; 95% CI, -22.1 to 6.1), or anatomic success at 24 months.
Two years after vaginal surgery for prolapse and stress urinary incontinence, neither ULS nor SSLF was significantly superior to the other for anatomic, functional, or adverse event outcomes. Perioperative BPMT did not improve urinary symptoms at 6 months or prolapse outcomes at 2 years.
clinicaltrials.gov Identifier: NCT00597935.
To determine the feasibility and case detection rate of a geographic information systems (GIS)-based integrated community screening strategy for tuberculosis, syphilis, and human immunodeficiency ...virus (HIV).
Prospective cross-sectional study of all participants presenting to geographic hot spot screenings in Wake County, North Carolina.
The residences of tuberculosis, HIV, and syphilis cases incident between 1/1/05-12/31/07 were mapped. Areas with high densities of all 3 diseases were designated "hot spots." Combined screening for tuberculosis, HIV, and syphilis were conducted at the hot spots; participants with positive tests were referred to the health department.
Participants (N = 247) reported high-risk characteristics: 67% previously incarcerated, 40% had lived in a homeless shelter, and 29% had a history of crack cocaine use. However, 34% reported never having been tested for HIV, and 41% did not recall prior tuberculin skin testing. Screening identified 3% (8/240) of participants with HIV infection, 1% (3/239) with untreated syphilis, and 15% (36/234) with latent tuberculosis infection. Of the eight persons with HIV, one was newly diagnosed and co-infected with latent tuberculosis; he was treated for latent TB and linked to an HIV provider. Two other HIV-positive persons had fallen out of care, and as a result of the study were linked back into HIV clinics. Of 27 persons with latent tuberculosis offered therapy, nine initiated and three completed treatment. GIS-based screening can effectively penetrate populations with high disease burden and poor healthcare access. Linkage to care remains challenging and will require creative interventions to impact morbidity.
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